Differential tolerance is induced in T cells recognizing distinct epitopes of myelin basic protein

Immunity. 1998 May;8(5):571-80. doi: 10.1016/s1074-7613(00)80562-2.

Abstract

Experimental allergic encephalomyelitis (EAE) is induced by T cell-mediated immunity to central nervous system antigens. In H-2u mice, EAE is mediated primarily by T cells specific for residues 1-11 of myelin basic protein (MBP). We demonstrate that differential tolerance to MBP1-11 versus epitopes in MBP121-150 is induced by expression of endogenous MBP, reflecting extreme differences in stability of peptide/MHC complexes. The diverse MBP121-150-specific TCR repertoire can be divided into three fine specificity groups. Two groups were identified in wild-type mice despite extensive tolerance, but the third group was not detected. Activated MBP121-150-specific T cells induce EAE in wild-type mice. Thus, encephalitogenic T cells that escape tolerance either recognize short-lived peptide/MHC complexes or express TCRs with unique specificities for stable complexes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Epitope Mapping*
  • Epitopes, T-Lymphocyte / immunology*
  • H-2 Antigens / immunology
  • Hybridomas
  • Immune Tolerance / immunology*
  • Immunoglobulin Variable Region / genetics
  • Mice
  • Mice, Inbred C3H
  • Myelin Basic Protein / immunology*
  • Peptide Fragments / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Sequence Analysis, DNA
  • T-Lymphocytes / immunology*

Substances

  • Epitopes, T-Lymphocyte
  • H-2 Antigens
  • Immunoglobulin Variable Region
  • Myelin Basic Protein
  • Peptide Fragments
  • Receptors, Antigen, T-Cell, alpha-beta